The viral cognate (v-fos) of proto-oncogene fos (c-fos) is the resident oncogene of FBJ murine osteosarcoma virus, which induces bone tumors. During its biogenesis the v-fos gene suffered a 104 bp out-of-frame deletion. Consequently, the v-fos and c-fos proteins have an altered reading frame at their C-termini. While both v-fos and c-fos proteins can induce cellular transformation, the latter is generally not synthesized in sustained amounts to inflict a transformed phenotype. The c-fos protein is transiently synthesized during normal cell growth and hematopoietic differentiation. To understand the role of proto-oncogene fos in normal cells, we plan to investigate in detail the nature and function of c-fos protein. Specifically, we plan to undertake the following experiments: 1) isolation and purification of c-fos protein from whole tissues; 2) expression of v-fos and c-fos proteins in yeast; 3) raise antisera to purified c-fos protein or synthetic peptides corresponding to c-fos protein; 4) raise monoclonal antibodies to c-fos protein; 5) study the post-translational modifications characteristic of c-fos protein; 6) determine the sub-nuclear localization of the fos protein; 7) since fos proteins associate with a cellular 39 kDa protein, we propose to partially purify p39 to obtain antisera; 8) the gene encoding p39 will be molecularly cloned and its structure analyzed; 9) recently a cDNA clone has been identified which shares some homology to c-fos gene. This related fos gene has been referred to as 'r-fos" gene. We plan to identify the nature of this protein. We hope that these studies will allow us to understand the role of c-fos protein in a normal cell. We can then devise effective strategies to combat its aberrant behavior.